Nosocomial infection (also known as hospital-acquired infection) is an infection whose development is favored by a hospital environment, such as one acquired by a patient during a hospital visit or one developing among hospital staff.
Nosocomial infections can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Many types are difficult to attack with antibiotics, and antibiotic resistance is spreading to bacteria that can infect people outside the hospital. Among the categories of bacteria most known to infect patients are MRSA (methicilin-resistant Staphylococcus aureus), a Gram-positive bacterium, and Acinetobacter baumannii, which is Gram-negative. Acinetobacter bacteria are evolving and becoming immune to existing antibiotics, including even last-resource antibacterials such as polymyxins. Another growing threat is the drug-resistant, Gram-negative Klebsiella pneumoniae, which can cause severe pneumonia and infections of the urinary tract, bloodstream, and other parts of the body. The membrane structures of these bacteria make them difficult to attack with antibiotics, so that antibiotic resistance is spreading, often due to bacteria that can infect people outside the hospital.
For nosocomial pneumonia, specifically, the pathogens are primarily MRSA, and antibiotic-resistant Gram-negatives, of which P. aeruginosa is typically most common.
Antibiotics with coverage against Gram-positive and Gram-negative organisms, including Pseudomonas, should be empirically assayed and then tailored according to the susceptibility pattern of the isolated organisms. Two-drug combinations (e.g. an antipseudomonal beta-lactam with an aminoglycoside) are often used.
P. aeruginosa, as mentioned above, is a major nosocomial pathogen responsible for severe chronic and acute infection, particularly one of the most frequent causes of ventilator-associated pneumonia and catheter related bloodstream infections. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week. Patients with acquired-immune deficiency syndrome (AIDS), burn wounds and cystic fibrosis present a high risk of developing P. aeruginosa infections posing a serious clinical challenge with sepsis mortalities as high as 60% in immunocompromised patients.
The opportunistic pathogens causing nosocomial infections, such as Pseudomonas aeruginosa, once established within the host are able to form biofilms, a sine qua non feature for the development of a variety of chronic infections. They are also able to form biofilms on the inert surfaces of medical devices of internal and external use. Biofilms, defined as microbial communities attached to an abiotic surface, represent an additional challenge to antimicrobial therapies. Biofilm formation is induced by genotypic and phenotypic changes of the planktonic microorganisms, ensuing in a multi-layered cell cluster structure coated by an external polysaccharide matrix; composed of polysaccharides, proteins and extracellular DNA. Once organized in biofilm structures pathogenic bacteria become more resistant to antibiotic agents and immune system clearance, requesting a more elaborated strategy for a successful treatment of associated infections. Therefore, there is an urgent need to develop effective antimicrobial strategies against both planktonic and biofilm forms of these pathogens.
Antimicrobial proteins and peptides (AMPs) are proposed as new alternative candidates to current treatments for biofilm associated infections. AMPs are small, amphipathic, and frequently cationic molecules, characterized by rapid, potent and broad-spectrum action against microorganisms.
Human RNases have been studied as a new potential source for developing alternative antimicrobial agents. Human RNase 3, also known as eosinophil cationic protein (ECP), is a small highly cationic protein (pl˜11) that is stored in the secondary granules of eosinophils. RNase 3 is secreted during the infection process where the protein exerts a high antimicrobial activity against a wide range of microorganisms, such as bacteria, viruses and parasites. Some ECP analogues have been studied with the aim of elucidating the amino acid residues with antimicrobial properties (Torrent M. et al. 2011).
Other antimicrobial peptides have been described as potent P. aeruginosa inhibitors. One such is LL-37, from the cathelicidin family, which presents a high interaction for the negatively charged bacterial membranes and LPS molecules and reported antimicrobial activity against planktonic P. aeruginosa. Furthermore, LL-37 is able to both inhibit P. aeruginosa biofilm formation and remove preformed P. aeruginosa biofilms (Nagant C. et al. 2012).
Secondly, the hybrid peptide cecropin A (1-7)-melittin(2-9), named CA-M, and resulting from the juxtaposition of residues (1-7) of cecropin A to residues (2-9) of melittin, is a potent antimicrobial against a wide variety of microorganisms. CA-M is a small, amphipathic and cationic peptide, with a high affinity to bacterial negatively charged membranes, exerting its antimicrobial action by pore formation (Saugar J. M. et al. 2006).
The beta-boomerang WY-12 peptide, adopts a particular β-stranded secondary structuration that resembles a boomerang upon LPS interaction and combines antimicrobial activity with LPS affinity (Bhunia A. et al. 2009).
Lastly, the human parotid secretory derived peptide GL-13 is devoid of antimicrobial activity but is able to induce P. aeruginosa agglutination (Gorr S. U. et al. 2008).
In spite of the existence of the above-mentioned potentially antimicrobial peptides, eradication of established biofilm communities of pathogen species is one of the pending challenges for the development of new antimicrobial agents. In particular, as already noted above, P. aeruginosa is of serious concern among nosocomial pathogens, for its tendency to form organized microbial communities posing enhanced resistance to conventional antibiotics.